Effects of Adenovirus-Mediated Hepatocyte Growth Factor Gene Therapy on Postinfarct Heart Function: Comparison of Single and Repeated Injections

Wang, Wei; Wang, Ming-Qi; Wang, Hao; Gao, Wei; Zhang, Zhen; Zhao, Shan; Xu, Hui-Zhi; Chen, Bin; Zhu, Meixiao; Wu, Chu-Tse; Yang, Jing; Wang, Sheng-Lian

doi:10.1089/hum.2015.119

Cited by 9 publications

(6 citation statements)

References 24 publications

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“…HGF is a multi-functional growth factor with anti-inflammatory and angiogenic activities [31]. Currently, clinical trials of the HGF gene therapy in the treatment of ischemic heart failure are ongoing [32]. Coupling the HGF gene therapy and cell therapy displayed a synergistic promoting effect on tissue regeneration and therapeutic angiogenesis.…”

Section: Discussionmentioning

confidence: 99%

Transplantation of HGF gene-engineered skeletal myoblasts improve infarction recovery in a rat myocardial ischemia model

et al. 2017

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BackgroundSkeletal myoblast transplantation seems a promising approach for the repair of myocardial infarction (MI). However, the low engraftment efficacy and impaired angiogenic ability limit the clinical efficiency of the myoblasts. Gene engineering with angiogenic growth factors promotes angiogenesis and enhances engraftment of transplanted skeletal myoblasts, leading to improved infarction recovery in myocardial ischemia. The present study evaluated the therapeutic effects of hepatocyte growth factor (HGF) gene-engineered skeletal myoblasts on tissue regeneration and restoration of heart function in a rat MI model.Methods and resultsThe skeletal myoblasts were isolated, expanded, and transduced with adenovirus carrying the HGF gene (Ad-HGF). Male SD rats underwent ligation of the left anterior descending coronary artery. After 2 weeks, the surviving rats were randomized into four groups and treated with skeletal myoblasts by direct injection into the myocardium. The survival and engraftment of skeletal myoblasts were determined by real-time PCR and in situ hybridization. The cardiac function with hemodynamic index and left ventricular architecture were monitored; The adenovirus-mediated-HGF gene transfection increases the HGF expression and promotes the proliferation of skeletal myoblasts in vitro. Transplantation of HGF-engineered skeletal myoblasts results in reduced infarct size and collagen deposition, increased vessel density, and improved cardiac function in a rat MI model. HGF gene modification also increases the myocardial levels of HGF, VEGF, and Bcl-2 and enhances the survival and engraftment of skeletal myoblasts.ConclusionsHGF engineering improves the regenerative effect of skeletal myoblasts on MI by enhancing their survival and engraftment ability.

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Section: Discussionmentioning

confidence: 99%

Transplantation of HGF gene-engineered skeletal myoblasts improve infarction recovery in a rat myocardial ischemia model

et al. 2017

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“…HGF administration was effective and safe in other preclinical studies [ 9 , 13 , 50 ]. Consequently, there are various clinical trials at present in which patients are recruited for assessment of HGF administration by different routes [ 51 ].…”

Section: Discussionmentioning

confidence: 99%

Intracoronary Administration of Microencapsulated HGF in a Reperfused Myocardial Infarction Swine Model

Blanco-Blázquez

Báez-Díaz

Sánchez-Margallo

et al. 2023

JCDD

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Therapy microencapsulation allows minimally invasive, safe, and effective administration. Hepatocyte growth factor (HGF) has angiogenic, anti-inflammatory, anti-apoptotic, and anti-fibrotic properties. Our objective was to evaluate the cardiac safety and effectiveness of intracoronary (IC) administration of HGF-loaded extended release microspheres in an acute myocardial infarction (AMI) swine model. An IC infusion of 5 × 106 HGF-loaded microspheres (MS+HGF, n = 7), 5 × 106 placebo microspheres (MS, n = 7), or saline (SAL, n = 7) was performed two days after AMI. TIMI flow and Troponin I (TnI) values were assessed pre- and post-treatment. Cardiac function was evaluated with magnetic resonance imaging (cMR) before injection and at 10 weeks. Plasma cytokines were determined to evaluate the inflammatory profile and hearts were subjected to histopathological evaluation. Post-treatment coronary flow was impaired in five animals (MS+HGF and MS group) without significant increases in TnI. One animal (MS group) died during treatment. There were no significant differences between groups in cMR parameters at any time (p > 0.05). No statistically significant changes were found between groups neither in cytokines nor in histological analyses. The IC administration of 5 × 106 HGF-loaded-microspheres 48 h post-AMI did not improve cardiac function, nor did it decrease inflammation or cardiac fibrosis in this experimental setting.

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“…Activation of the c-Met receptor further activates many intracellular signalling pathways, including RAS-mitogen activated protein kinase, signal transducer and activator of transcription, phosphatidylinositol-3 kinase, protein kinase B, mammalian target of rapamycin, and β-catenin pathway [33,34]. Our group has previously shown that HGF therapy could promote cardiac repair and improve cardiac function in MI rats through the above mechanisms [35].…”

Section: Discussionmentioning

confidence: 99%

Gene Therapy with Hepatocyte Growth Factor Improves Left Ventricular Systolic Function After Myocardial Infarction: A Systematic Review and Meta-analysis of Pig Models

Du¹,

Chen²,

Wang³

et al. 2020

Preprint

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Background: Hepatocyte growth factor (HGF) is an angiogenic cytokine which can promote angiogenesis and inhibit fibrosis. Previous studies have shown that HGF may have significant therapeutic effects on ischaemic diseases, such as ischaemic heart disease and peripheral arterial occlusive disease. Due to insufficient clinical study evidence, we conducted a quantitative meta-analysis of HGF therapy in pigs with myocardial infarction (MI) to provide more reliable evidence for the feasibility and effectiveness of HGF therapy for MI patients. We also analysed the efficacy and characteristics of different gene therapy vectors and drug delivery routes.Methods: PubMed, EMBASE, and the China National Knowledge Infrastructure were searched for randomised studies that corresponded to our subject. The search terms included (hepatocyte growth factor OR HGF) AND (heart failure OR HF OR myocardial infarction OR MI OR AMI OR coronary heart disease OR CHD). The retrieved articles were screened strictly according to the inclusion criteria. The endpoints were the left ventricular ejection fraction (LVEF) and capillary density in the ischaemic regions in the model pigs.Results: A total of nine studies were eventually included in this meta-analysis. Our analysis showed that LVEF (with mean difference [MD]:9.73, 95%CI :8.70, 10.76, P < 0.00001) and capillary density (MD:79.98, 95%CI :24.58,135.39, P=0.005) in the HGF group were significantly higher than those in the control group several weeks after HGF treatment. Further analysis showed that there was no statistically significant difference in the improvement of LVEF caused by intracoronary adenovirus5-mediated HGF (Ad5-HGF) gene transfer and intramyocardial plasmid HGF injection (12.63±3.2 vs 9.4±1.09, P=0.06), while intramyocardial injection of plasmid HGF had a stronger angiogenic capacity than intramyocardial administration of Ad5-HGF and HGF in hydrogel (117.34±27.82 vs 26.45±22.11 vs 11.50±5.28, P＜0.00001).Conclusions: HGF therapy can effectively promote angiogenesis and recovery of cardiac function and is a promising cardiac repair method. Intracoronary Ad5 vector transfer and intramyocardial injection of plasmid vectors can be used as effective means of gene therapy, and hydrogel as a vector also has potential applications.

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Effects of Adenovirus-Mediated Hepatocyte Growth Factor Gene Therapy on Postinfarct Heart Function: Comparison of Single and Repeated Injections

Cited by 9 publications

References 24 publications

Transplantation of HGF gene-engineered skeletal myoblasts improve infarction recovery in a rat myocardial ischemia model

Transplantation of HGF gene-engineered skeletal myoblasts improve infarction recovery in a rat myocardial ischemia model

Intracoronary Administration of Microencapsulated HGF in a Reperfused Myocardial Infarction Swine Model

Gene Therapy with Hepatocyte Growth Factor Improves Left Ventricular Systolic Function After Myocardial Infarction: A Systematic Review and Meta-analysis of Pig Models

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